Mastering the most up-to-date treatment in practice today requires the ability to recall not only available and emerging treatment options, but also strategies and response assessment approaches for high-risk patients, which includes treatment options for patients with comorbidities. Most importantly, practitioners must then safely and effectively translate this knowledge into patient-specific management plans, factoring in the patients’ comorbidities, age, and previous treatment history. This activity is designed to provide an evidenced-based overview addressing how community practitioners may navigate the ever-increasing number of highly effective options for approaching newly diagnosed multiple myeloma in patients who present with – or develop – comorbidities associated with their disease.